Anti-adhesion molecule therapy in Theiler's murine encephalomyelitis virus-induced demyelinating disease.
We examined the role of leukocyte function-associated antigen (LFA)-1 and its counter-receptor intercellular adhesion molecule (ICAM)-1, one of the most important pairs of adhesion molecules, in the development of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Immunohistochemical study showed hyper-expression of ICAM-1 on vascular endothelial cells and expression of LFA-1 on mononuclear infiltrating cells in the spinal cords of TMEV-infected mice. Treatment with mAb to ICAM-1 and/or LFA-1 molecules resulted in significant suppression of the development of demyelinating disease, both clinically and histologically, with down-regulation in the CNS of the respective adhesion molecules after treatment. In mice treated with these mAb, the specific delayed-type hypersensitivity and T cell proliferative responses for TMEV were decreased. The production of tumor necrosis factor-alpha and IFN-gamma in spleen cells was also decreased, but IL-4 production remained unchanged. These data suggest that ICAM-1/LFA-1 interaction is critically involved in the pathogenesis of TMEV-IDD and that antibodies to these adhesion molecules could be a novel therapeutic approach to the treatment of demyelinating diseases such as human multiple sclerosis.
Inoue
A
A
Third Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Koh
C S
CS
Yamazaki
M
M
Ichikawa
M
M
Isobe
M
M
Ishihara
Y
Y
Yagita
H
H
Kim
B S
BS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000096:biosynthesis; D000918:Antibody Specificity; D016207:Cytokines / Q000096:biosynthesis; D003711:Demyelinating Diseases / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000821:virology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology* / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology* / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D011051:Poliomyelitis / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology; D017945:Theilovirus
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D016207:Cytokines; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1